© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Comparison of the effects of supplementation with whey mineral and potassium on arterial tone in experimental hypertension
aUniversity of Tampere, Department of Pharmacological Sciences, P.O. Box 607, FIN-33101 Tampere, Finland
bResearch and Development Centre, Valio Ltd, Helsinki, Finland
cDepartment of Pharmacology and Toxicology, University of Helsinki, Helsinki, Finland
dDepartment of Clinical Chemistry, Tampere University Hospital, Tampere, Finland
eDepartment of Pediatrics, Tampere University Hospital, Tampere, Finland
fDepartment of Clinical Physiology, Tampere University Hospital, Tampere, Finland
gDepartment of Internal Medicine, Tampere University Hospital, Tampere, Finland
hDepartment of Medicine, Helsinki University Hospital, Helsinki, Finland
iDepartment of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, Oulu, Finland
* Corresponding author. Tel.: +358-3-215-6111; Fax: +358-3-215-6170; E-mail: blilpo@uta.fi
Objective: The aim of this work was to compare the effects of supplementation of rat chow diet with potassium (K+) and whey mineral concentrate (Whey), a diet rich in milk minerals, on blood pressure and arterial responses in vitro in spontaneously hypertensive rats (SHR). Methods: Thirty young SHR and twenty Wistar–Kyoto rats (WKY) were allocated into five groups: SHR, Whey-SHR, K+-SHR, WKY and Whey-WKY. Whey-supplementation was performed by adding 25% whey mineral concentrate to the chow, which in particular increased the intake of potassium (from 1.0% to 3.6%) and also that of calcium (from 1.0% to 1.3%) and magnesium (from 0.2% to 0.3%) in the rats. The K+-SHR were given extra potassium chloride (KCl) so that the final potassium content in the chow was 3.6%. Blood pressures were measured indirectly by the tail-cuff method. Responses of mesenteric arterial rings were examined in standard organ chambers after 12 study weeks. Results: During the 12-week study systolic blood pressures in control SHR increased steadily from 160 to about 230 mmHg, while supplementation with either Whey or potassium had a clear antihypertensive effect of about 50 mmHg in the hypertensive rats. Blood pressures in the WKY and Whey-WKY groups remained comparable during the whole study. In noradrenaline-precontracted arterial rings, endothelium-dependent relaxations to acetylcholine (ACh), as well as endothelium-independent relaxations to nitroprusside and isoprenaline were attenuated in untreated SHR, while all these dilatory responses were similarly improved by Whey and potassium supplementation. The cyclooxygenase inhibitor diclofenac, which reduces the synthesis of dilatory and constricting prostanoids, clearly enhanced the relaxation to ACh in untreated SHR, but was without effect in the other groups. In the presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester the relaxation to ACh was markedly reduced in all SHR groups, whereas in the two WKY groups, distinct relaxations to ACh were still present. The remaining responses were partially prevented by tetraethylammonium, an inhibitor of calcium-activated potassium channels, and the difference between untreated and potassium-supplemented SHR was abolished. When endothelium-mediated hyperpolarization of smooth muscle was prevented by precontracting the preparations with 50 mM KCl, only marginal differences were observed in relaxations to ACh between untreated SHR and the other groups. Interestingly, the impaired endothelium-independent relaxations to cromakalim, a hyperpolarizing vasodilator acting via ATP-sensitive potassium channels, were normalized by Whey mineral and potassium diets. Conclusion: Supplementation with Whey mineral and a comparable dose of potassium similarly opposed the development of experimental genetic hypertension, an effect which was associated with improved arterial dilatory properties. Both supplements augmented the hyperpolarization-related component of arterial relaxation, increased the sensitivity of smooth muscle to nitric oxide, and decreased the production of vasoconstrictor prostanoids. Therefore, the beneficial effects of the Whey diet could be attributed to increased intake of potassium in SHR.
KEYWORDS ANP; Arterial smooth muscle; Blood pressure; Dietary potassium; Dietary sodium; Endothelium; Hyperpolarization; Spontaneously hypertensive rat
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